Gene expression analysis of Fmr1-KO mouse caudate putamen reveals new preclinical biomarkers for fragile X syndrome
- 1Scantox Neuro GmbH
- 2Institute for Biology, Karl-Franzens University of Graz
- 3BioDoks e. U.
Abstract
Background: Fragile X syndrome is a monogenic cause of autism spectrum disorder. Fmr1 -KO mice are a well-known model for the disease, and the model’s behavioral phenotype has been well-characterized. Unfortunately, translational molecular tissue biomarkers for this model remain sparse.
Methods: To identify new molecular biomarkers, we performed a gene sequencing analysis of caudate putamen tissue of Fmr1 -KO mice at the age of 7 weeks. RNA sequencing analysis revealed 13 genes to be upregulated and 37 genes to be downregulated in the caudate putamen of Fmr1 -KO mice. The two most upregulated genes were necdin ( Ndn ) and insulin degrading enzyme ( Ide ). Upregulation of Ndn and Ide genes was confirmed by real-time PCR. NDN protein expression was analyzed in the caudate putamen, hippocampus, and brainstem using immunofluorescent labeling. A co-labeling experiment assessed NDN expression in cholinergic neurons. Ide gene upregulation and its effect on insulin levels were evaluated, and protein expression analysis focused on NDN, parvalbumin, and myelin basic protein in the caudate putamen, cortex, and hippocampus.
Results: mRNA levels of Ndn and Ide and protein levels of NDN and IDE were strongly upregulated in the caudate putamen of Fmr1 -KO mice. NDN protein expression was also increased in the hippocampus and brainstem, with partial expression observed in cholinergic neurons. Upregulated Ide gene expression was associated with reduced insulin levels in Fmr1 -KO mice.
Conclusion: NDN and IDE emerge as promising candidates for preclinical disease-relevant biomarkers in Fmr1 -KO mice. Future research needs to demonstrate whether disease-modulating drugs can alter the expression profile of these proteins and ultimately alleviate disease symptoms.
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BibTeX
@article{sharghi2026gene,
title = {{Gene expression analysis of Fmr1-KO mouse caudate putamen reveals new preclinical biomarkers for fragile X syndrome}},
author = {Shirin Sharghi and Stefanie Flunkert and Magdalena Daurer and Livia Breznik and Boris Philippe Chagnaud and Manuela Prokesch},
journal = {Frontiers in Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnins.2026.1833413},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1833413/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gene expression analysis of Fmr1-KO mouse caudate putamen reveals new preclinical biomarkers for fragile X syndrome
AU - Shirin Sharghi
AU - Stefanie Flunkert
AU - Magdalena Daurer
AU - Livia Breznik
AU - Boris Philippe Chagnaud
AU - Manuela Prokesch
PY - 2026
DA - 2026/10/23
JO - Frontiers in Neuroscience
DO - 10.3389/fnins.2026.1833413
UR - https://www.frontiersin.org/articles/10.3389/fnins.2026.1833413/full
AB - Background: Fragile X syndrome is a monogenic cause of autism spectrum disorder. Fmr1 -KO mice are a well-known model for the disease, and the model’s behavioral phenotype has been well-characterized. Unfortunately, translational molecular tissue biomarkers for this model remain sparse. Methods: To identify new molecular biomarkers, we performed a gene sequencing analysis of caudate putamen tissue of Fmr1 -KO mice at the age of 7 weeks. RNA sequencing analysis revealed 13 genes to be upregulated and 37 genes to be downregulated in the caudate putamen of Fmr1 -KO mice. The two most upregulated genes were necdin ( Ndn ) and insulin degrading enzyme ( Ide ). Upregulation of Ndn and Ide genes was confirmed by real-time PCR. NDN protein expression was analyzed in the caudate putamen, hippocampus, and brainstem using immunofluorescent labeling. A co-labeling experiment assessed NDN expression in cholinergic neurons. Ide gene upregulation and its effect on insulin levels were evaluated, and protein expression analysis focused on NDN, parvalbumin, and myelin basic protein in the caudate putamen, cortex, and hippocampus. Results: mRNA levels of Ndn and Ide and protein levels of NDN and IDE were strongly upregulated in the caudate putamen of Fmr1 -KO mice. NDN protein expression was also increased in the hippocampus and brainstem, with partial expression observed in cholinergic neurons. Upregulated Ide gene expression was associated with reduced insulin levels in Fmr1 -KO mice. Conclusion: NDN and IDE emerge as promising candidates for preclinical disease-relevant biomarkers in Fmr1 -KO mice. Future research needs to demonstrate whether disease-modulating drugs can alter the expression profile of these proteins and ultimately alleviate disease symptoms.
SN - 1662-453X
SN - 1662-4548
ER -